The human genome sequencing project provides the foundation for using individual genetics to optimize the selection and dosing of medications. The field of pharmacogenomics is still young, but has undergone a revolution in the last decade, as genomic technologies have uncovered associations between drug response phenotypes and genetic variations. The challenge now is to define the mechanisms underlying these associations, to advance our detailed understanding of the genetics of drug response. The PharmGKB (http://www.pharmgkb.org/) is devoted to collecting, encoding and disseminating knowledge about pharmacogenomics. PharmGKB is the pre-eminent resource for information about genes involved in the pharmacokinetics (PK) and pharmacodynamics of drug response, the pathways in which they act, and their important polymorphisms. PharmGKB staff curate this information, and have also helped lead successful international data sharing initiatives. In this proposal, we outline a plan to (1) curate information about genetic variations, pathways and networks relevant to drug response (2) create informatics tools for understanding the mechanism of drug response, (3) create and support new data sharing consortia, (4) engage in strategic collaborations to maximize PharmGKB's impact, and (5) disseminate the PharmGKB resources to the scientific community. We provide testimonials from users and letters of support from the research community to demonstrate our ongoing impact on the field. RELEVANCE (See instructions): Pharmacogenomics is the study of how variations in human genes affect our response to drugs. It is the science behind personalized medicine-using individual genetics to increase the efficacy of drugs, and reduce their unwanted side effects. This proposal outlines a plan to extend the PharmGKB, a web-based resource that provides high-quality information and tools to researchers in pharmacogenomics.